chr14-92071010-C-CCTGCTGCTGCTG
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_004993.6(ATXN3):c.915_916insCAGCAGCAGCAG(p.Gln302_Gln305dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0087 ( 24 hom., cov: 20)
Exomes 𝑓: 0.0053 ( 165 hom. )
Failed GnomAD Quality Control
Consequence
ATXN3
NM_004993.6 inframe_insertion
NM_004993.6 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.168
Genes affected
ATXN3 (HGNC:7106): (ataxin 3) Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 14-92071010-C-CCTGCTGCTGCTG is Benign according to our data. Variant chr14-92071010-C-CCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 931861.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00866 (1234/142494) while in subpopulation AFR AF= 0.0202 (734/36306). AF 95% confidence interval is 0.019. There are 24 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1227 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN3 | NM_004993.6 | c.915_916insCAGCAGCAGCAG | p.Gln302_Gln305dup | inframe_insertion | 10/11 | ENST00000644486.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN3 | ENST00000644486.2 | c.915_916insCAGCAGCAGCAG | p.Gln302_Gln305dup | inframe_insertion | 10/11 | NM_004993.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00862 AC: 1227AN: 142384Hom.: 24 Cov.: 20
GnomAD3 genomes
?
AF:
AC:
1227
AN:
142384
Hom.:
Cov.:
20
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00534 AC: 7015AN: 1314362Hom.: 165 Cov.: 92 AF XY: 0.00515 AC XY: 3384AN XY: 657202
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
7015
AN:
1314362
Hom.:
Cov.:
92
AF XY:
AC XY:
3384
AN XY:
657202
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00866 AC: 1234AN: 142494Hom.: 24 Cov.: 20 AF XY: 0.00861 AC XY: 596AN XY: 69228
GnomAD4 genome
?
AF:
AC:
1234
AN:
142494
Hom.:
Cov.:
20
AF XY:
AC XY:
596
AN XY:
69228
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Azorean disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Nov 16, 2018 | This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: A. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at